Phaeocystis antarctica is an integral player of the phytoplankton community of the Southern Ocean (SO), the world’s largest high-nutrient low-chlorophyll region, and faces chronic iron (Fe) limitation. As the SO is responsible for 40% of anthropogenic CO2 uptake, P. antarctica must also deal with ocean acidiﬁcation (OA). However, mechanistic studies investigating the effects of Fe limitation and OA on trace metal (TM) stoichiometry, transcriptomic, and photophysiological responses of this species, as well as on the Fe chemistry, are lacking. This study reveals that P. antarctica responded strongly to Fe limitation by reducing its growth rate and particulate organic carbon (POC) production. Cellular concentrations of all TMs, not just Fe, were greatly reduced, suggesting that Fe limitation may drive cells into secondary limitation by another TM. P. antarctica was able to adjust its photophysiology in response to Fe limitation, resulting in similar absolute electron transport rates across PSII. Even though OA-stimulated growth in Fe-limited and -replete treatments, the slight reduction in cellular POC resulted in no net effect on POC production. In addition, relatively few genes were differentially expressed due to OA. Finally, this study demonstrates that, under our culture conditions, OA did not affect inorganic Fe or humic-acid-like substances in seawater but triggered the production of humic-acid-like substances by P. antarctica. This species is well adapted to OA under all Fe conditions, giving it a competitive advantage over more sensitive species in a future ocean.